Valuing the cost of improving Chilean primary vaccination: a cost minimization analysis of a hexavalent vaccine.

BACKGROUND: The phased withdrawal of oral polio vaccine (OPV) and the introduction of inactivated poliovirus vaccine (IPV) is central to the polio 'end-game' strategy. METHODS: We analyzed the cost implications in Chile of a switch from the vaccination scheme consisting of a pentavalent vaccine with whole-cell pertussis component (wP) plus IPV/OPV vaccines to a scheme with a hexavalent vaccine with acellular pertussis component (aP) and IPV (Hexaxim®) from a societal perspective. Cost data were collected from a variety of sources including national estimates and previous vaccine studies. All costs were expressed in 2017 prices (US$ 1.00 = $Ch 666.26). RESULTS: The overall costs associated with the vaccination scheme (4 doses of pentavalent vaccine plus 1 dose IPV and 3 doses OPV) from a societal perspective was estimated to be US$ 12.70 million, of which US$ 8.84 million were associated with the management of adverse events related to wP. In comparison, the cost associated with the 4-dose scheme with a hexavalent vaccine (based upon the PAHO reference price) was US$ 19.76 million. The cost of switching to the hexavalent vaccine would be an additional US$ 6.45 million. Overall, depending on the scenario, the costs of switching to the hexavalent scheme would range from an additional US$ 2.62 million to US$ 6.45 million compared with the current vaccination scheme. CONCLUSIONS: The switch to the hexavalent vaccine schedule in Chile would lead to additional acquisition costs, which would be partially offset by improved logistics, and a reduction in adverse events associated with the current vaccines.

[Epiglottitis due to Haemophilus influenzae type b in the vaccination era: pediatric clinical case]. / Epiglotitis por Haemophilus influenzae tipo b en la era de la vacunación: caso clínico pediátrico.

Acute infectious epiglottitis is infrequent at present due to vaccination for its main etiologic agent, Haemophilus influenzae b (Hib). It must be taken into account when we make a differential diagnosis in a child whose clinical symptoms are respiratory distress, stridor, dysphonia and fever. We report a 2-year-old child, previously healthy, whose vaccination calendar was complete, and whose clinical presentation included respiratory distress and stridor; at the moment of the intubation the laryngoscopy showed an acute epiglottitis. Blood cultures were taken, which were positive for Hib. He was treated with ceftriaxone during 13 days, and the control blood cultures and cerebrospinal fluid were negative.

La epiglotitis aguda infecciosa es infrecuente en la actualidad, debido a la vacunación contra su principal agente etiológico, el Haemophilus influenzae b. Se requiere alto índice de sospecha ante el cuadro clínico de dificultad respiratoria, estridor, disfonía y fiebre. Se presenta a un niño de 2 años, previamente sano, con esquema de vacunas completas, con dificultad respiratoria aguda y estridor laríngeo, en el que, al momento de realizar la intubación, se realizó el diagnóstico de epiglotitis aguda. Con hemocultivos positivos para Haemophilus influenzae b, cumplió 13 días de tratamiento con ceftriaxona, con hemocultivos de control y cultivo de líquido cefalorraquídeo negativo.

Vaccination herd effect experience in Latin America: a systematic literature review.

BACKGROUND: National pediatric vaccination programs have been introduced in Latin America (LatAm) to reduce the burden of diseases due to pathogens such as rotavirus, Haemophilus influenzae type b (Hib) and pneumococcus. Vaccination health benefits may extend to unvaccinated populations by reducing pathogen transmission. Understanding herd effect is important for implementation and assessment of vaccination programs. The objective was to conduct a systematic review of published epidemiological evidence of herd effect with Hib, rotavirus and pneumococcal conjugate vaccines (PCV) in LatAm. METHODS: Searches were conducted in PubMed, Virtual Health Library (VHL), SciELO and SCOPUS databases, for studies reporting data on herd effect from Hib, rotavirus and PCV vaccination in LatAm, without age restriction. Searches were limited to articles published in English, Spanish or Portuguese (1990-2016). After screening and full-text review, articles meeting the selection criteria were included to be critically appraised following criteria for observational and interventional studies. The presence of a herd effect was defined as a significant decrease in incidence of disease, hospitalization, or mortality. RESULTS: 3,465 unique articles were identified, and 23 were included (Hib vaccine n = 5, PCV n = 8, rotavirus vaccine n = 10). Most studies included children and/or adolescents (age range varied between studies). Studies in adults, including older adults (aged > 65 years), were limited. Few studies reported statistically significant reductions in disease incidence in age groups not targeted for vaccination. Hib-confirmed meningitis hospitalization decreased in children but herd effect could not be quantified. Some evidence of herd effect was identified for PCV and rotavirus vaccine in unvaccinated children. Evidence for herd effects due to PCV in adults was limited. CONCLUSION: After introduction of Hib, PCV and rotavirus vaccination in LatAm, reductions in morbidity/mortality have been reported in children not targeted for vaccination. However, due to methodological limitations (e.g. short post-vaccination periods and age range studied), there is currently insufficient evidence to quantify the herd effect in adult populations. More research and higher quality surveillance is needed to characterize herd effect of these vaccines in LatAm.

Immunogenicity and safety of MenACWY-TT, a meningococcal conjugate vaccine, co-administered with routine childhood vaccine in healthy infants: A phase III, randomized study.

BACKGROUND: Invasive meningococcal disease has a high burden in young children, particularly during infancy. We investigated the immunogenicity and safety of a quadrivalent meningococcal conjugated vaccine (MenACWY-TT) co-administered with routine vaccines in healthy infants. METHODS: In this phase IIIb study (NCT01340898) conducted in 2 centers in Lebanon and Mexico, 750 infants were randomized (2:1:1) to receive MenACWY-TT according to 3 schedules: 3+1 (at ages 2, 4, 6 and 15-18 months; group ACWY3+1); 1+1 (at 6 and 15-18 months; group ACWY1+1) or single-dose at 15-18 months (group ACWY1). All infants received PHiD-CV and DTPa-IPV/Hib at ages 2, 4, 6, 15-18 months. Immune responses to MenACWY-TT were assessed by rSBA and hSBA at 7 months (groups ACWY3+1, ACWY1+1) and pre- and post-vaccination at 15-18 months of age (all groups). Immune responses to co-administered vaccines, reactogenicity and safety were also evaluated. RESULTS: Immunogenicity of MenACWY-TT at 1 month post-primary vaccination was demonstrated in group ACWY3+1: the lower limit of the 95% confidence interval for the percentage of infants with rSBA titers ≥8 was >80% for each serogroup. At 7 months of age, ≥93.9% of MenACWY-TT-primed infants had rSBA titers ≥8. Post-MenACWY-TT vaccination at age 15-18 months, ≥96.3% of participants in all groups had rSBA titers ≥8, regardless of the number of doses received previously. The percentage of infants with hSBA titers ≥4 were ≥87.2% and ≥89.7% at post-primary and booster/single-dose vaccination, respectively. Immune responses to PHiD-CV and DTPa-IPV/Hib did not seem impacted by co-administration with MenACWY-TT in infancy. The incidence of all adverse events was similar among groups. Serious adverse events were reported for 63/750 children in all groups; none were considered vaccine-related by investigators. CONCLUSION: Primary vaccination with 3 or 1 dose(s) of MenACWY-TT when co-administered with routine pediatric vaccines in infants is immunogenic and well-tolerated.

New insights about functional and cross-reactive properties of antibodies generated against recombinant TbpBs of Haemophilus parasuis.

Vaccines have become fundamental in the control and elimination of Glässer Disease, a systemic disease of pigs caused by Haemophilus parasuis. The classic vaccines available for prevention of this infection were developed without a robust knowledge about host immunological mechanisms. In this study, we demonstrated the presence of cross-reactive epitopes on both the N-lobe and C-lobe of variants of transferrin binding protein B (TbpBs) expressed on the surface of 6 virulent serovars of H. parasuis. Antibodies against TbpB-derived antigens were capable of increasing the phagocytic capacity of neutrophils and were also capable of blocking porcine transferrin from binding to TbpB. Surprisingly, none of the pig or mice antisera from animals immunized with TbpB-derived antigens mixed with Montanide IMS 2215 VG PR adjuvant were able to activate the classical complement pathway (CCP). In contrast, antisera from mice immunized with TbpB-derived antigens adjuvanted with Freund's adjuvants or Montanide Gel 01 were able to activate the CCP and kill H. parasuis. Our results demonstrate that the type of adjuvant can modulate the functional response induced by TbpB-derived antigens. Based on these results, we propose that a properly formulated TbpB-based vaccine may elicit a functional protective antibody response with broad cross-reactivity against heterologous strains of H. parasuis.

Efficacy of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine against acute otitis media and nasopharyngeal carriage in Panamanian children - A randomized controlled trial.

We previously reported 10-valent pneumococcal non-typeable Haemophilus influenzae (NTHi) protein D conjugate vaccine (PHiD-CV) efficacy in a double-blind randomized trial (ClinicalTrials.gov: NCT00466947) against various diseases, including acute otitis media (AOM). Here, we provide further analyses. In the Panamanian subset, 7,359 children were randomized (1:1) to receive PHiD-CV or control vaccine at age 2/4/6 and 15-18 months. Of these, 2,000 had nasopharyngeal swabs collected. AOM cases were captured when parents sought medical attention for children with AOM symptoms; surveillance was enhanced approximately 2 y into the study through regular telephone calls or home visits by study personnel, who advised parents to visit the clinic if their child had AOM symptoms. Mean follow-up was 31.4 months. Clinical AOM (C-AOM) cases were assessed by physicians and confirmed by otorhinolaryngologists. Middle ear fluid samples, taken from children with C-AOM after specific informed consent, and nasopharyngeal samples were cultured for pathogen identification. For 7,359 children, 2,574 suspected AOM cases were assessed by a primary healthcare physician; 649 cases were C-AOM cases as per protocol definition. From the 503 MEF samples collected, 158 resulted in a positive culture. In the intent-to-treat cohort (7,214 children), PHiD-CV showed VE against first C-AOM (24.0% [95% CI: 8.7, 36.7]) and bacterial (B-AOM) episodes (48.0% [20.3, 66.1]) in children <24 months, which declined thereafter with age. Pre-booster VE against C-AOM was 30.7% [12.9, 44.9]; post-booster, -6.7% [-36.4, 16.6]. PHiD-CV VE was 17.7% [-6.1, 36.2] against moderate and 32.7% [-20.5, 62.4] against severe C-AOM. VE against vaccine-serotype pneumococcal NPC was 31.2% [5.3, 50.3] 3 months post-booster, and 25.6% [12.7, 36.7] across all visits. NTHi colonization rates were low and no significant reduction was observed. PHiD-CV showed efficacy against C-AOM and B-AOM in children younger than 24 months, and reduced vaccine-serotype NPC.

Síndrome de Nicolau por la administración de la vacuna séxtuple intramuscular en un lactante de 6 meses / Nicolau syndrome induced by intramuscular injection of a hexavalent vaccine in a 6-month-old girl

El síndrome de Nicolau, también conocido como embolia cutis medicamentosa o dermatitis livedoide, es una reacción cutánea infrecuente, caracterizada por una necrosis de la piel y los tejidos blandos de aparición súbita luego de la aplicación intramuscular de algunas drogas. Presentamos a un bebé de 6 meses de edad que, al recibir la tercera dosis de la vacuna séxtuple intramuscular, desarrolló una lesión necrótica con reticulado violáceo periférico en el sitio de aplicación. Se destaca la importancia del diagnóstico precoz a fin de instaurar un adecuado tratamiento y seguimiento para evitar complicaciones secundarias a la isquemia.

Nicolau syndrome, also known as embolia cutis medicamentosa or livedo-like dermatitis, is a sudden tissue necrosis, a rare complication of intramuscular injection of some drugs. We report a case of a 6-month-old girl who received intramuscularly the third dose of hexavalent vaccine (DTaP-HVB-IPV/HIb), and immediately presented a livedoid lesion around the injection site, progressing to necrosis. We reinforce the importance of early diagnosis to perform a suitable treatment and clinical follow-up to avoid ischemic secondary complications.

Immunogenicity and Safety of a Booster Injection of DTap-IPV//Hib (Pentaxim) Administered Concomitantly With Tetravalent Dengue Vaccine in Healthy Toddlers 15-18 Months of Age in Mexico: A Randomized Trial.

BACKGROUND: The live, attenuated, tetravalent dengue vaccine (CYD-TDV) is licensed in a number of dengue endemic countries for individuals ≥9 years of age. Before the integration of any vaccine into childhood vaccination schedules, a lack of immune interference and acceptable safety when coadministered with other recommended vaccines should be demonstrated. METHODS: This randomized, multi-center phase III trial was conducted in Mexico. Healthy toddlers (n = 732) received a booster dose of a licensed pentavalent combination vaccine [diphtheria, tetanus, acellular pertussis, inactivated polio vaccine and Haemophilus influenzae type b (DTaP-IPV//Hib)] either concomitantly or sequentially, with the second dose of CYD-TDV administered as a 3-dose schedule. Antibody titers against diphtheria toxoid, tetanus toxoid and pertussis antigens were measured by enzyme-linked immunosorbent assay. Antibodies against poliovirus and dengue serotypes were measured using a plaque reduction neutralization test. Noninferiority was demonstrated for each of the DTaP-IPV//Hib antigens if the lower limit of the 2-sided 95% confidence interval of the difference in seroconversion rates between the 2 groups (CYD-TDV and placebo) was ≥10%. Safety of both vaccines was assessed. RESULTS: Noninferiority in immune response was demonstrated for all DTaP-IPV//Hib antigens. After 3 doses of CYD-TDV, no difference was observed in the immune response for CYD-TDV between groups. There were no safety concerns during the study. CONCLUSION: Coadministration of the DTaP-IPV//Hib booster vaccine with CYD-TDV has no observed impact on the immunogenicity or safety profile of the DTaP-IPV//Hib booster vaccine. No difference was observed on the CYD-TDV profile when administered concomitantly or sequentially with the DTaP-IPV//Hib booster vaccine.

[Nicolau syndrome induced by intramuscular injection of a hexavalent vaccine in a 6-month-old girl]. / Síndrome de Nicolau por la administración de la vacuna séxtuple intramuscular en un lactante de 6 meses.

Nicolau syndrome, also known as embolia cutis medicamentosa or livedo-like dermatitis, is a sudden tissue necrosis, a rare complication of intramuscular injection of some drugs. We report a case of a 6-month-old girl who received intramuscularly the third dose of hexavalent vaccine (DTaP- HVB-IPV/HIb), and immediately presented a livedoid lesion around the injection site, progressing to necrosis. We reinforce the importance of early diagnosis to perform a suitable treatment and clinical follow-up to avoid ischemic secondary complications.

El síndrome de Nicolau, también conocido como embolia cutis medicamentosa o dermatitis livedoide, es una reacción cutánea infrecuente, caracterizada por una necrosis de la piel y los tejidos blandos de aparición súbita luego de la aplicación intramuscular de algunas drogas. Presentamos a un bebé de 6 meses de edad que, al recibir la tercera dosis de la vacuna séxtuple intramuscular, desarrolló una lesión necrótica con reticulado violáceo periférico en el sitio de aplicación. Se destaca la importancia del diagnóstico precoz a fin de instaurar un adecuado tratamiento y seguimiento para evitar complicaciones secundarias a la isquemia.

Innate Immune Factors in Mothers' Breast Milk and Their Lack of Association With Rotavirus Vaccine Immunogenicity in Nicaraguan Infants.

To better understand underlying causes of lower rotavirus vaccine effectiveness in low-middle income countries (LMICs), we measured innate antiviral factors in Nicaraguan mothers' milk and immune response to the first dose of the pentavalent rotavirus vaccine in corresponding infants. No relationship was found between concentrations of innate factors and rotavirus vaccine response.

Use of rapid needs assessment as a tool to identify vaccination delays in Guatemala and Peru.

OBJECTIVE: To explore the use of rapid needs assessment (RNA) surveys to determine the prevalence and factors contributing to delays in vaccination of children in two low middle-income countries (LMIC). METHODS: Data from two RNA surveys performed as part of program improvement evaluations in Guatemala and Peru were used for this analysis. The primary endpoint was the timeliness of immunization with delay defined as administration of vaccines beyond 28 days from recommended age for DTwP-HepB-Hib (Penta) and measles-mumps-rubella (MMR) vaccines, as well as past age-restrictions for rotavirus vaccine. Independent risk factors analyzed included child's gender, birth year, number of children in household, maternal age, maternal education, and food insecurity. RESULTS: Vaccine information was available from 811 children from 838 households surveyed. High rate of immunization delays was observed, with 75.6% of children in Guatemala and 57.8% of children in Peru being delayed for the third dose of Penta primary series. Factors associated with delayed vaccination in Guatemala included advanced maternal age and increased number of children in household. In Peru, significant associations were birth year before 2009, lower maternal education level, and increased number of children in household. CONCLUSIONS: RNA is a fast and effective method to identify timely vaccine coverage and derive a hypothesis of factors possibly associated with vaccination delay.

Internações sensíveis à atenção primária específicas de mulheres / Sensitive female-specific hospitalization in primary care

Objetivou-se analisar as internações por condições sensíveis à atenção primária (ICSAP) específicas em mulheres e os fatores que determinam ou influenciam a ocorrência dessas internações (fatores socioeconômicos, sociodemográficos e controle de saúde) por meio de um inquérito de morbidade hospitalar realizado com amostra de 429 mulheres internadas em hospitais conveniados ao Sistema Único de Saúde. O percentual de ICSAP foi 49,42% (n = 212), com destaque para as internações específicas do sexo feminino 19,35% (n = 83). Associaram ao risco de internar por CSAP: idade superior a 60 anos, baixa escolaridade, internação prévia, realização de controle regular de saúde, falta de vínculo com a Estratégia Saúde da Família (ESF) e ser gestante. As causas evidentes foram as condições relacionadas à gravidez, ao parto e ao puerpério e às inflamações nos órgãos pélvicos femininos. Os resultados sugerem falhas no atendimento ambulatorial que deveria ser oportuno e resolutivo no contexto da saúde da mulher.

The scope of this paper was to analyze female-specific sensitive hospitalization occurring in primary care conditions and factors that determine or affect the occurrence of such hospitalizations (social, economic and demographic factors; health control). Analysis was performed by surveys on hospital morbidity with a sample of 429 females attended in Unified Health System (SUS) contracted hospitals. The sensitive hospitalizations percentage in primary care reached 49.42% (n = 212), highlighting female-specific hospitalization at 19.35% (n = 83). Hospitalization risks comprised elderly people over sixty, low schooling, previous hospitalizations, normal health control, lack of association with the Family Health Strategy and pregnancy. Evident causes were related to conditions of pregnancy, childbirth, post-partum and inflammations of the female pelvic organs. Results suggested flaws in outpatient attendance that should be adequate and provide solutions in women’s health.

Vaccine schedule compliance among very low birth weight infants in Lima, Peru.

OBJECTIVE: There is little information about vaccine schedule compliance in very-low-birth-weight infants in developing countries. The aim of the study was to describe the compliance with the vaccine schedule among this population in Lima, Peru. PATIENTS AND METHODS: We conducted a prospective cohort study in four hospitals in Lima in infants with a birth-weight of less than 1500 g, followed from birth up to 12 months of age every 2 weeks. The date and age at administration of each vaccine was recorded RESULTS: 222 infants were enrolled. The median birth-weight was 1250 g (range 550-1499 g) and the median gestational age was 30.0 weeks (range 23-37 weeks). The mean age for the first pentavalent (DPT, Hib, HepB) and oral polio vaccine administration was 4.3 ± 1.4 months in infants with a birth-weight of < 1000 g vs. 3.1 ± 1.0 in infants with a birth-weight 1000-1500 g (p < 0.001); 4.1 ± 0.9 vs. 3.3 ± 1.1 for rotavirus (p < 0.05); and 5.1 ± 2.1 vs. 4.3 ± 1.8 for the 7-valent pneumococcal conjugated vaccine. Only 35% had received the three doses of oral polio and pentavalent vaccine by seven months, although by nine months 81% had received these vaccines. CONCLUSIONS: Vaccination of very-low-birth-weight infants in Peru is significantly delayed, especially in infants with a birth-weight of < 1000 g and lower gestational age. Urgent educational interventions targeting physicians and nurses should be implemented in order to improve vaccination rates and timing in these high risk populations.

Changes in hospitalizations for pneumonia after universal vaccination with pneumococcal conjugate vaccines 7/13 valent and haemophilus influenzae type b conjugate vaccine in a Pediatric Referral Hospital in Uruguay.

BACKGROUND: In 1994, Uruguay included Haemophilus influenzae b (Hib) conjugated vaccine in a 3 + 1 schedule. In March 2008, 7-valent pneumococcal conjugate vaccines (PCV7) was included in a 2 +1 schedule. In 2010, 13-valent PCV replaced PCV7. Catch-up immunization was offered. The aim of this study was to describe the etiology of community-acquired pneumonia (CAP) in children 0-14 years of age hospitalized at the Hospital Pediatrico-Centro Hospitalario Pereira Rossell between 2003 and 2012. METHODS: Annual hospitalization rates (per 10,000 discharges) for CAP and bacterial-confirmed CAP in children 0-14 years of age was described prior PCV7 vaccination (2003-2007), during the year of implementation of PCV7 (2008) and after the introduction of PCV7 (2009-2012). Data regarding age, strains isolated from pleural fluid and/or blood, vaccination status, pneumococcal and H. influenzae serotypes were obtained from Hospital Pediatrico-Centro Hospitalario Pereira Rossell databases and vaccination records. RESULTS: Hospitalization rates for CAP and pneumococcal CAP between prevaccine years and the last year after introduction of vaccination with PCV (2012) significantly decreased by 78.1% and 92.4%, respectively. Significant reduction for 13-valent PCV vaccine serotypes and significant increase for nonvaccine serotypes was observed. A decrease in Staphylococcus aureus pneumonia was observed. Hospitalization rates for H. influenzae CAP remain stable before and after pneumococcal vaccination. CONCLUSIONS: Three years after PCV7/13 introduction into the routine vaccination schedule, there was a rapid and significant reduction in rates of CAP and P-CAP. An increase of etiology of CAP by other agents was not observed.

Evaluation of the effectiveness of Haemophilus influenzae type b conjugate vaccine introduction against radiologically-confirmed hospitalized pneumonia in young children in Ukraine.

OBJECTIVE: Haemophilus influenzae type b (Hib) conjugate vaccine was included into the national vaccination schedule of Ukraine in 2006. The objective of this study was to demonstrate the effectiveness of Hib conjugate vaccine against radiologically-confirmed hospitalized pneumonia in children. STUDY DESIGN: Children <2 years old with radiologically confirmed pneumonia admitted to 11 participating hospitals in Kiev and Dnepropetrovsk between April 2007 and June 2009 were included in a case-control evaluation. Four controls were matched to each case by date of birth (within 14 days) and outpatient clinic. We estimated ORs for vaccination and vaccine effectiveness ((1 - OR)*100%) using conditional logistic regression, adjusting for comorbid conditions and contraindications for vaccination. RESULTS: We enrolled 188 case-children and 735 controls. Median age was 16 months (range 4-24 months). Fifty-one percent of cases and 67% of controls received ≥1 doses of Hib conjugate vaccine; 26% of cases and 37% of controls received ≥3 doses. The effectiveness of ≥1 dose Hib conjugate vaccine was estimated at 45% (95% CI 18%-63%). CONCLUSIONS: Our study showed that Hib infections are important causes of hospitalized radiologically confirmed pneumonia in young children in Ukraine.

Haemophilus influenzae type b disease among children in rural Mozambique: impact of vaccine introduction.

OBJECTIVE: Haemophilus influenzae type b (Hib) conjugate vaccine has dramatically reduced invasive Hib disease worldwide. Yet, data on protection against pneumonia and among children with HIV are limited. We evaluated the impact of Hib conjugate vaccine introduction in 2009 in a rural, high-HIV prevalence area in Mozambique. STUDY DESIGN: From 2006-2011, we conducted hospital-based surveillance for invasive Hib disease and clinical pneumonia (classified as severe and very severe) among children <5 years of age. Incidences calculated using population denominators were compared between baseline (2006-2008) and post-Hib conjugate vaccine (2010-2011) periods. Surveillance data for radiologically-confirmed pneumonia among children <2 years of age in 2011 were compared with baseline data from 2004-2006. RESULTS: Among 50 cases of invasive Hib disease, 5 occurred after Hib conjugate vaccine introduction; 1 case-patient was age-eligible for Hib conjugate vaccine (and had received 3 doses). Four post-Hib conjugate vaccine case-patients (including Hib conjugate vaccine failure) had HIV. Among children <1 and <5 years of age, significant reductions occurred in rates of invasive Hib disease (91% and 85%, respectively) and very severe pneumonia (29% and 34%, respectively). Radiologically-confirmed pneumonia incidence fell significantly (33%) in children <2 years of age. Severe pneumonia incidence did not decline. CONCLUSIONS: We demonstrate important reductions in invasive disease and pneumonia following Hib conjugate vaccine introduction in a high-HIV area. Continued surveillance is needed to monitor long-term Hib conjugate vaccine effects, particularly among children with HIV.

Incidence of radiologically-confirmed pneumonia and Haemophilus influenzae type b carriage before Haemophilus influenzae type b conjugate vaccine introduction in Central Vietnam.

OBJECTIVES: To determine the incidence of radiologically-confirmed pneumonia (RCP) and Haemophilus influenzae type b (Hib) carriage in central Vietnam as a baseline data before Hib conjugate vaccine introduction. STUDY DESIGN: In the context of ongoing population-based prospective, hospitalized acute respiratory infection surveillance study, a cross-sectional Hib carriage study was conducted among 1000 children < 5 years of age living in NhaTrang, Vietnam in June 2010, 1 month before the nationwide introduction of Hib conjugate vaccine in Vietnam. RESULTS: The incidence of RCP hospitalizations among children < 5 years of age was 3.3 per 1000 children. The highest incidence was observed among children 12-23 month age group (8.3 per 1000). Haemophilus influenzae carriage was detected in 37% of the children and Hib carriage rate was 3%. Eighty-two percent of the Haemophilus influenzae had TEM ß-lactamase resistance gene. The presence of 6 or more family members was associated with an increased rate of Hib carriage (P = .04). CONCLUSIONS: Incidence of RCP and Hib carriage in this cross-sectional survey are lower compared with other studies. Continued surveillance for invasive Hib disease and sequential Hib carriage surveys are needed to support future assessments of the impact of Hib conjugate vaccine in Vietnam.

Incidence of Haemophilus influenzae type b disease in The Gambia 14 years after introduction of routine Haemophilus influenzae type b conjugate vaccine immunization.

OBJECTIVE: Haemophilus influenzae type b (Hib) conjugate vaccine was first introduced in Africa in The Gambia in 1997 as a primary 3-dose course in infancy with no booster, and was followed by the disappearance of invasive Hib disease by 2002. A cluster of cases detected non-systematically in post-infant children in 2005-2006 raised the question of the need for a booster dose. The objective of this study was to determine the incidence of invasive Hib disease in Gambian children 14 years after the introduction of Hib conjugate vaccine. STUDY DESIGN: This hospital-based clinical and microbiological Hib disease surveillance in 3 hospitals in the western region of The Gambia was undertaken between October 2007 and December 2010 applying the same methods used in a previous Hib vaccine effectiveness study in 1997-2002. RESULTS: The annual incidences of Hib meningitis and all invasive Hib disease in children aged <5 years remained below 5 cases per 100,000 children during 2008-2010. The median age of patients with any invasive Hib disease was 5 months. CONCLUSION: Hib conjugate vaccination as a primary 3-dose course in The Gambia remains highly effective in controlling invasive Hib disease, and current data do not support the introduction of a booster dose.

Cost-effectiveness of Haemophilus influenzae type b conjugate vaccine in low- and middle-income countries: regional analysis and assessment of major determinants.

OBJECTIVES: To estimate the cost-effectiveness of Haemophilus influenzae type b (Hib) conjugate vaccine in low- and middle-income countries and identify the model variables, which are most important for the result. STUDY DESIGN: A static decision tree model was developed to predict incremental costs and health impacts. Estimates were generated for 4 country groups: countries eligible for funding by the GAVI Alliance in Africa and Asia, lower middle-income countries, and upper middle-income countries. Values, including disease incidence, case fatality rates, and treatment costs, were based on international country estimates and the scientific literature. RESULTS: From the societal perspective, it is estimated that the probability of Hib conjugate vaccine cost saving is 34%-53% in Global Alliance for Vaccines and Immunization eligible African and Asian countries, respectively. In middle-income countries, costs per discounted disability adjusted life year averted are between US$37 and US$733. Variation in vaccine prices and risks of meningitis sequelae and mortality explain most of the difference in results. For all country groups, disease incidence cause the largest part of the uncertainty in the result. CONCLUSIONS: Hib conjugate vaccine is cost saving or highly cost-effective in low- and middle-income settings. This conclusion is especially influenced by the recent decline in Hib conjugate vaccine prices and new data revealing the high costs of lost productivity associated with meningitis sequelae.